CN110680908B - Soluble microneedle of rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine and preparation method thereof - Google Patents
Soluble microneedle of rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine and preparation method thereof Download PDFInfo
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- CN110680908B CN110680908B CN201810720838.6A CN201810720838A CN110680908B CN 110680908 B CN110680908 B CN 110680908B CN 201810720838 A CN201810720838 A CN 201810720838A CN 110680908 B CN110680908 B CN 110680908B
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- 108010060123 Conjugate Vaccines Proteins 0.000 title claims abstract description 51
- 229940031670 conjugate vaccine Drugs 0.000 title claims abstract description 51
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- 238000002360 preparation method Methods 0.000 title description 11
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- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
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- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/095—Neisseria
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
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- Dermatology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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Abstract
The invention provides a soluble microneedle of a rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine, which consists of polyvinylpyrrolidone, a disintegrating agent, superfine calcium carbonate and A group C meningococcal polysaccharide conjugate vaccine; wherein the solid content of the disintegrating agent in the needle body is 6-16%, the solid content of the superfine calcium carbonate in the needle body is 5-20%, and the solid content of the group A and group C meningococcal polysaccharide conjugate vaccine in the needle body is not higher than 10%. The soluble microneedle provided by the invention not only improves the drug release rate of the microneedle, but also avoids the technical defect of poor skin penetration effect of the needle body caused by rapid drug release; meanwhile, the immunological experiment result proves that the immune effect generated by the micro needle is superior to that of subcutaneous injection, and the micro needle can effectively generate immune protection effect on organisms.
Description
Technical Field
The invention relates to the technical field of microneedle administration of vaccines, and provides a soluble microneedle of a rapidly-disintegrating A-group C-group meningococcal polysaccharide conjugate vaccine and a preparation method thereof.
Background
Epidemic cerebrospinal meningitis is suppurative meningitis caused by meningococci, also known as epidemic meningitis. The main clinical manifestations are fever, headache, vomiting, skin stasis and cervical rigidity, and the like, and the cerebrospinal fluid is changed suppuratively. The epidemic cerebrospinal meningitis vaccine on the market at present is in the form of injection, and the vaccine is also used for infants, and the injection has the defect of poor compliance. Thus, a new route of vaccine administration is needed. Human skin contains abundant antigen presenting cells, for example, langerhans cells in epidermis account for 3-5% of all epidermis cells, so that transdermal immunization has better research prospect. However, the stratum corneum disorder of the skin makes delivery of macromolecular drugs a difficult problem.
The soluble micro needle belongs to the micro needle category, can overcome the stratum corneum obstruction of human skin, can well promote the transdermal absorption of macromolecular antigen medicine, and realizes painless administration. Unlike other microneedles, the soluble microneedles can be automatically dissolved after being penetrated into human skin, so that the problems of breakage of the needle head in the skin of the solid microneedles, small drug loading rate of the coated microneedles and the like are avoided, and the method is a popular field of current microneedle research.
The Chinese patent with publication number of CN107158368A discloses a brain-epidemic polysaccharide conjugate vaccine soluble microneedle patch and a preparation method thereof, and the following paragraph is written from the [ 0042 ] section of the document: the needle body of the microneedle patch can release target drugs into the skin within 15-60 min; and, only 30min can ensure that the soluble microneedle needle body penetrating into the skin part is completely dissolved in the skin and the A+C group cephalopolypolysaccharide conjugate vaccine is released into the skin. Also, when the patient is actually self-administered, the microneedle must be kept pressed against the skin for 30min before it is removed, which results in poor patient compliance.
Therefore, it is considered to develop a soluble microneedle capable of completely releasing the group a-group C meningococcal polysaccharide conjugate vaccine into the skin in a shorter time, so as to solve the defect of poor patient compliance in the prior art.
At present, no patent literature report exists that the disintegrating agent can be added into the soluble micro needle to carry out quick release of the medicine, and the applicant of the invention discovers in the early pre-experiment that the disintegrating agent can improve the quick release of the medicine of the micro needle and has the technical defect that the needle body is difficult to effectively penetrate into the skin due to weaker mechanical strength.
In summary, how to develop a soluble microneedle of a rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine, which can improve the drug release rate after the microneedle is inserted into the skin and solve the problem of patient compliance; but also can ensure that the skin is penetrated with enough mechanical strength, even can improve the immune response effect of the vaccine microneedle, and is a technical problem which is urgently needed to be solved by the technicians in the field.
Disclosure of Invention
The invention aims to provide a soluble microneedle of a rapidly disintegrating type A group C group meningococcal polysaccharide conjugate vaccine and a preparation method thereof, and the bottleneck existing in the prior art is solved by adding a disintegrating agent and superfine calcium carbonate in a proper proportion as a mechanical strength enhancing phase.
In order to realize the development thought, the technical scheme adopted by the invention is as follows:
a soluble microneedle of a rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine, wherein the microneedle consists of polyvinylpyrrolidone, a disintegrating agent, superfine calcium carbonate and A group C meningococcal polysaccharide conjugate vaccine; wherein the solid content of the disintegrating agent in the needle body is 6-16%, the solid content of the superfine calcium carbonate in the needle body is 5-20%, and the solid content of the group A and group C meningococcal polysaccharide conjugate vaccine in the needle body is not higher than 10%.
Preferably, the disintegrating agent is selected from one or more of dry starch, sodium carboxymethyl starch, low-substituted cellulose and crosslinked sodium carboxymethyl cellulose,
more preferably, the disintegrant is sodium carboxymethyl starch.
Preferably, the solid content ratio of each component in the needle body is as follows: PVP accounts for 70%, carboxymethyl starch accounts for 10%, superfine calcium carbonate accounts for 10%, and A group C group meningococcal polysaccharide conjugate vaccine accounts for 10%.
The invention also provides a preparation method of the soluble microneedle of the rapidly disintegrating A group C group meningococcal polysaccharide conjugate vaccine, which adopts a dry powder compression molding method and comprises the following steps: filling the material with the prescription amount into a female die, stamping and demoulding to obtain the flaky microneedle array.
In the invention, the superfine calcium carbonate is used as a mechanical strength enhancing phase, so that the mechanical strength of the microneedle can be greatly improved, and the skin penetrating capability of the microneedle can be enhanced.
Compared with the prior art, the soluble microneedle patch for the rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine has the innovation that:
the microneedle adopts the technology of combining the disintegrating agent and the superfine calcium carbonate, improves the drug release rate of the microneedle (the drug is completely released within 3 min), and avoids the technical defect of poor effect of penetrating the skin of the needle body caused by rapid drug release; meanwhile, the immunological experiment result proves that the immune effect generated by the micro needle is superior to that of subcutaneous injection, and the micro needle can effectively generate immune protection effect on organisms.
Detailed Description
In order to enable those skilled in the art to better understand the present invention, the technical solutions in the present embodiment will be specifically described below. It should be noted that the following examples are only for illustrating the present invention, and not for limiting the present invention, and any modifications and changes made to the present invention within the spirit of the present invention and the scope of the appended claims fall within the scope of the present invention.
Example 1: dry powder compression molding method for preparing soluble micro needle
The soluble microneedle of the group A and group C meningococcal polysaccharide conjugate vaccine is prepared by the following steps: uniformly mixing the meningococcal polysaccharide conjugate vaccine of group A and group C, polyvinylpyrrolidone (PVP), a disintegrating agent and superfine calcium carbonate according to a prescription proportion (the average particle size of the materials is smaller than 0.5 mu m), filling into a female die with a conical micropore array with fixed specification size (the array parameters are that the depth of holes is 900 mu m, the diameter of each hole is 300 mu m, the pitch of the hole array is 900 mu m, and the total number of holes is 100 in 10 multiplied by 10), punching, and demoulding to obtain the flaky microneedle array.
Example 2: influence of different matrix materials on dissolution rate of microneedle bodies
In order to compare the dissolution rate differences of the microneedle bodies prepared from different matrix materials, several matrix materials, namely polyvinylpyrrolidone PVP, PVA, HA, CMC, methyl vinyl ether-maleic anhydride copolymer (Gantrez) and dextran, were selected for investigation.
0.5% (w.t.) methylene blue was added, a drug-free sheet-like microneedle array was prepared by the method of example 1, and each microneedle was immersed in physiological saline, and the time was started, and the time required for complete dissolution of the needle was observed with a magnifying glass, and the results are shown in Table 1.
Table 1. Dissolution Rate comparison of matrix materials for each needle (mean+ -SD, n=5)
| Needle matrix material | Time(s) required for complete dissolution of needle |
| PVP | 20±3 |
| PVA | 205±16 |
| HA | 51±6 |
| CMC | 236±19 |
| Gantrez | 78±8 |
| Dextran | 46±5 |
From the results shown in Table 1, it is found that PVP is most rapidly dissolved in the matrix material, and thus the present invention is preferably used, and further differences in effects of other components are examined.
Example 3: influence of different disintegrants on dissolution rate of microneedle needles
In order to compare the influence of the addition of different disintegrants on the dissolution rate of the microneedle body, the effects of several disintegrants of dry starch, sodium carboxymethyl starch, low-substituted cellulose and croscarmellose sodium were examined.
PVP was used as a needle tip solution, 0.5% (w.t.) methylene blue was added to the needle material, and the disintegrants in Table 2 were added so that the solid content of the final disintegrants in the needle was 10% (w.t.).
A tablet-shaped microneedle array containing no drug was prepared by the method of example 1, and each microneedle was immersed in physiological saline, and the time was counted, and the time required for complete dissolution of the needle was observed with a magnifying glass, and the results are shown in Table 2.
Table 2 comparison of dissolution rates of different disintegrants (mean±sd, n=5)
| Disintegrating agent | Time(s) required for complete dissolution of needle |
| Control group | 20±3 |
| Dry starch | 17±3 |
| Sodium carboxymethyl starch | 7±1 |
| Low substituted cellulose | 15±2 |
| Croscarmellose sodium | 12±3 |
From the results of Table 2, it is understood that 4 kinds of disintegrants have a certain improvement in the dissolution rate of the microneedle needles, and sodium carboxymethyl starch has the best effect, and thus are preferable in the present invention, and further differences in the effects of other components are examined on the basis of the results.
Example 4: comparison of skin penetration effect and intradermal dissolution time for microneedles with different mechanical enhancing phase materials
The micro-needle needs proper hardness when penetrating into the skin, and the nano-material belongs to one of mechanical reinforcing phases, namely, the nano-particles are added into the organic high polymer polymerization of the soluble micro-needle to form the polymer-based nano-composite material so as to enhance the integral mechanical strength of the micro-needle. Regarding the combination of nanomaterials and soluble microneedles, it has been reported in the literature that, for example, researchers (Yu W, jiang, liu D, et al publication of biodegradable composite microneedles based on calcium sulfate and gelatin for transdermal delivery of insulin [ J ]. Materials Science and Engineering:c,2017, 71:725-734) add nanomaterial calcium sulfate hemihydrate powder to gelatin to form nanocomposite microneedles, enhancing the mechanical strength of the microneedles, making them useful for transdermal delivery of insulin; in addition, researchers (Yan L, raphall A P, zhu X, et al Nanocomposite-Strengthened Dissolving Microneedles for Improved Transdermal Delivery to Human Skin [ J ]. Advanced healthcare materials,2014,3 (4): 555-564) have added layered double hydroxides to carboxymethyl cellulose to form nanocomposite microneedles, which also enhance the mechanical strength of the microneedles, making them useful for transdermal delivery of ovalbumin. No report has been found of ultrafine calcium carbonate as a soluble microneedle nano-reinforcing phase.
In order to more fully reflect the skin penetration effect of the soluble microneedle, the present embodiment refers to example 2 of chinese patent No. CN107158368A, which selects gelatin as a simulated in vitro skin model, and examines the difference of the effects of three materials, i.e., double metal hydroxide, calcium sulfate hemihydrate, and ultrafine calcium carbonate, as the nano reinforcing phase. A sheet-like microneedle array was produced according to the method of example 1 in accordance with the proportions of the components in Table 3.
Skin penetration depth and dissolution time of microneedles the microneedles were inserted into skin models by the method described in example 2 of chinese patent No. CN107158368A, and the depth of microneedle insertion and the time required for the needle to completely dissolve in the part of the skin penetrated by the needle were observed by laser confocal observation, and the results are shown in table 3.
TABLE 3 skin penetration effect and intradermal dissolution time comparison of different nanoreinforcement phase materials (mean+ -SD, n=5)
According to pre-experiments and experience, the penetration depth of the soluble micro needle reaches more than 600 mu m, and the expected effect of the preparation can be achieved only when the dissolution time is less than 5min, so that the application requirements are met. From the results in Table 3, it can be seen that:
1) Analysis of groups a and B showed that PVP blank microneedles effectively penetrated the skin ex vivo, with the addition of 10% polysaccharide conjugate vaccine, the mechanical properties decreased, penetration depth was greatly reduced to 405 μm and intradermal dissolution increased to 18.4min, consistent with the description of example 2 of patent CN107158368A, thus limiting vaccine content to no more than 8% in patent CN 107158368A.
2) Analysis group C showed that when 10% of the disintegrant was added, the penetration depth was further reduced to 316 μm and the dissolution time was reduced to 3.1min, indicating that the disintegrating effect of the disintegrant was also well developed intradermally, but the mechanical properties of the microneedles were reduced after the addition of the disintegrant.
3) Analysis of group D, group E and group F shows that after different nano-reinforcement phases are added into the microneedles, the penetration depth of the microneedles is improved, but only group F (added with superfine calcium carbonate) meets the use requirement; moreover, the microneedle needles of group F penetrating into the skin can completely collapse the explanation drug within 3min, and the drug release speed is far better than that of the microneedle needles of the invention described in the paragraph [ 0042 ] of the patent CN107158368A, which is 15-60min, so that the superfine calcium carbonate is selected as the mechanical reinforcing phase material of the invention.
Example 5: effect of polysaccharide conjugate vaccine solids content variation on skin safety
In order to determine the solid content of the group A and group C meningococcal polysaccharide conjugate vaccine (hereinafter referred to as polysaccharide conjugate vaccine), the solid content of sodium carboxymethyl starch and superfine calcium carbonate is assumed to be a fixed value, the solid content of the polysaccharide conjugate vaccine is changed, and the effect difference caused by the change of the drug loading rate is examined.
Microneedle administration was performed by selecting skin on the back of a rabbit shaved, and 20min after microneedle application, and red swelling of skin at the microneedle application was observed, and as a result, it was found that: when the solid content of the polysaccharide conjugate vaccine is within 10%, no obvious skin red and swelling is generated after the solid content is more than 10%, and the irritation is high, so the solid content of the polysaccharide conjugate vaccine is not higher than 10%.
Example 6: influence of content variation of sodium carboxymethyl starch and superfine calcium carbonate on dissolution speed of microneedle body
Based on examples 2 to 5, assuming that the solid content of the polysaccharide conjugate vaccine is a certain value, the influence of the content change of sodium carboxymethyl starch or superfine calcium carbonate on the penetration depth and dissolution rate of the microneedle body was examined, and the results are shown in Table 4.
Table 4 solids content range screening of sodium carboxymethyl starch and ultrafine calcium carbonate (mean±sd, n=5)
According to pre-experiments and experience, the penetration depth of the soluble micro needle reaches more than 600 mu m, and the expected effect of the preparation can be achieved only when the dissolution time is less than 5min, so that the application requirements are met. From the results in table 4, it can be seen that:
1) Analysis groups A-E show that when the solid content of polysaccharide conjugate vaccine and superfine calcium carbonate is a fixed value, and the content of sodium carboxymethyl starch is increased from 5% to 17%, the mechanical property of the microneedle is reduced, and the penetration depth of the needle body is gradually reduced; taking the penetration depth and the dissolution time into comprehensive consideration, and when the content of sodium carboxymethyl starch is 6% -16%, the prepared microneedle meets the use requirement.
2) The analysis groups F-I show that when the solid content of the polysaccharide conjugate vaccine and the carboxymethyl starch sodium is a fixed value and the content of the superfine calcium carbonate is 5-20%, the penetration depth and the dissolution time of the prepared micro-needle meet the use requirements.
3) Comprehensively considering the penetration depth and the dissolution time, wherein the group C is an optimal prescription, namely the solid content ratio of each component in the microneedle body is as follows: 70% of polyvinylpyrrolidone (PVP), 10% of polysaccharide conjugate vaccine, 10% of sodium carboxymethyl starch and 10% of superfine calcium carbonate.
Example 7: comparison of mouse immune Effect
Female mice of 4-6 weeks of age BALB/c were selected, and the adaptive feeding and quarantine period was 3 days. Mice were randomly divided into 6 groups of 6 mice each, each group being stained with picric acid to distinguish the groups and prevent confusion during feeding and dosing, according to the grouping conditions in table 5. Wherein, 6 experimental groups are specifically as follows:
the control group 1 was an injection group of physiological saline injected subcutaneously with 0.2ml at 0,14,28 days at a physiological saline injection dose of 10 μg/dose as a blank control;
the injection group is an injection group of polysaccharide conjugate vaccine, 0.2ml is injected subcutaneously in 0,14,28 days, and the injection dosage of the polysaccharide conjugate vaccine is 10 mug/dose;
control group 2 was a soluble microneedle group without polysaccharide conjugate vaccine, prepared as a blank with reference to example 1;
the microneedle group A is a soluble microneedle group containing polysaccharide conjugate vaccine but not containing sodium carboxymethyl starch and superfine calcium carbonate, and the preparation method is as shown in the example 1, and the dosage of the polysaccharide conjugate vaccine is 10 mug/dose;
the microneedle group B is a soluble microneedle group containing polysaccharide conjugate vaccine and sodium carboxymethyl starch, but not containing superfine calcium carbonate, and the preparation method is as shown in the example 1, wherein the dosage of the polysaccharide conjugate vaccine is 10 mug/dose;
the microneedle group C is a soluble microneedle group containing polysaccharide conjugate vaccine, sodium carboxymethyl starch and superfine calcium carbonate, namely an optimal prescription group, and the preparation method refers to the example 1, and the dosage of the polysaccharide conjugate vaccine is 10 mug/dose;
the microneedle array A, B, C was used to remove hair from the skin on both sides of the back of the mice one day before administration, and the hair removal site was administered on the back for 0,14,28 days, and the sheet-like microneedle array was pressed against the skin surface for 3min, and the microneedles were removed and immunized 3 times throughout.
On day 35 of immunization of the mice, the mice were collected from the eyeballs after removal, and left at 37℃for 1 hour and then left at 4℃overnight. Placing in a centrifuge, centrifuging at 3000rpm for 8min, collecting serum, refrigerating at 2-8deg.C, separating serum, preserving at-20deg.C, and measuring antibody titer by ELISA, wherein the results are shown in Table 5.
Table 5. Antibody titre results for each group (mean.+ -. SD, n=6)
| Group of | Group A antibody titre (mIU/ml) | Group C antibody titre (mIU/ml) |
| Control group 1 | 0 | 0 |
| Control group 2 | 0 | 0 |
| Injection group | 12874±957 | 13609±1077 |
| Microneedle group A | 754±61 | 681±70 |
| Microneedle group B | 1378±125 | 1566±138 |
| Microneedle group C | 37618±2048 | 42893±3189 |
As can be seen from the results in table 5,
1) The microneedle group A only contains 10% of vaccine, so that the penetration effect is poor, and the vaccine is only released in a small amount within 3min, so that the titer of the generated group A antibodies is only about 1/17 of that of an injection group, and the titer of the generated group C antibodies is only about 1/20 of that of the injection group;
2) The micro needle group B is added with the disintegrating agent, so that the release amount of the vaccine is more than that of the group A, the antibody titer is higher than that of the group A, but the release amount is still different from that of the injection group;
3) The microneedle group C contains superfine calcium carbonate and a disintegrating agent, so that the penetrating effect and the drug release rate are good, the titer of the generated group A antibody is about 2.9 times that of an injection group, and the titer of the group C antibody is about 3.1 times that of the injection group.
In conclusion, the soluble microneedle of the group A and group C meningococcal polysaccharide conjugate vaccine prepared by the invention can completely release medicine within 3min after the microneedle is applied, and the superfine calcium carbonate is added to ensure that the microneedle can penetrate into skin with enough strength, so that the immunological experimental result proves that the immune effect generated by the microneedle is superior to that of subcutaneous injection, and the effect is obvious.
Claims (6)
1. A soluble microneedle of a rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine is characterized in that the needle comprises the following components in percentage by weight: 70% of polyvinylpyrrolidone, 10% of carboxymethyl starch sodium, 10% of superfine calcium carbonate and 10% of group A and group C meningococcal polysaccharide conjugate vaccine.
2. A soluble microneedle of a rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine is characterized in that the needle comprises the following components in percentage by weight: 74% of polyvinylpyrrolidone, 6% of carboxymethyl starch sodium, 10% of superfine calcium carbonate and 10% of group A and group C meningococcal polysaccharide conjugate vaccine.
3. A soluble microneedle of a rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine is characterized in that the needle comprises the following components in percentage by weight: polyvinylpyrrolidone accounts for 64%, carboxymethyl starch accounts for 16%, superfine calcium carbonate accounts for 10%, and group A and group C meningococcal polysaccharide conjugate vaccine accounts for 10%.
4. A soluble microneedle of a rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine is characterized in that the needle comprises the following components in percentage by weight: 75% of polyvinylpyrrolidone, 10% of carboxymethyl starch sodium, 5% of superfine calcium carbonate and 10% of group A and group C meningococcal polysaccharide conjugate vaccine.
5. A soluble microneedle of a rapidly disintegrating type A group and C group meningococcal polysaccharide conjugate vaccine is characterized in that the needle comprises the following components in percentage by weight: 60% of polyvinylpyrrolidone, 10% of carboxymethyl starch sodium, 20% of superfine calcium carbonate and 10% of group A and group C meningococcal polysaccharide conjugate vaccine.
6. A method for preparing a soluble microneedle of a rapidly disintegrating group a C meningococcal polysaccharide conjugate vaccine according to any one of claims 1 to 5, wherein a dry powder compression molding method is adopted, comprising the steps of: filling the material with the prescription amount into a female die, stamping and demoulding to obtain the flaky microneedle array.
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| CN107158368A (en) * | 2017-05-11 | 2017-09-15 | 广州新济药业科技有限公司 | Epidemic meningitis polysaccharide conjugate vaccine solubility microneedle patch and preparation method thereof |
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| Fabrication of composite microneedles integrated with insulin-loaded CaCO3 microparticles and PVP for transdermal delivery in diabetic rats;Depeng Liu等;Materials Science & Engineering C;180-188 * |
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